Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

Key Points

  • 20–40% of patients with IBD in Western countries are obese

  • Premorbid obesity, in particular visceral adiposity, might increase the risk of developing Crohn's disease

  • Obesity might contribute to the pathogenesis of IBD through dysbiosis, mucosal barrier dysfunction with bacterial translocation and activation of adipocytes

  • Risk of complications, such as surgery, hospitalization and infection, might be increased in patients with IBD who are obese

  • Obesity is associated with rapid clearance of biologic agents, resulting in low trough concentrations, and could result in suboptimal response to biologics

  • Treating obesity could be a potential adjunct therapeutic target in patients with IBD who are obese

Abstract

Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15–40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

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Figure 1: Association between premorbid obesity, waist–hip ratio and weight gain since age 18 years and IBD risk.
Figure 2: Postulated pathogenesis and feedback loop between visceral adipose tissue and intestinal inflammation in IBD.

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Acknowledgements

S.S. is supported by the NIH/National Library of Medicine training grant T15LM011271, the American College of Gastroenterology Junior Faculty Development Award and the Crohn's and Colitis Foundation of American Career Development Award. P.S.D. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases training grant 5T32DK007202. A.Z. has received support from NIH K08 DK102902, the American Association for the Study of Liver Diseases Liver Scholar Award, and the American Gastroenterological Association Microbiome Junior Investigator Research Award. The Authors thank L. J. Prokop, Senior Medical Librarian at Mayo Clinic, Rochester, USA, who assisted with a systematic literature review on this topic.

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S.S. and P.S.D. researched data for the article. S.S., P.S.D., A.Z., S.R. and W.J.S. substantially contributed to the discussion of content for the article. S.S. and P.S.D. wrote the article, and all authors contributed equally to reviewing and editing of the manuscript before submission.

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Correspondence to Siddharth Singh.

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W.J.S. has received consulting fees from Abbvie, Janssen Biotech, Prometheus Laboratories and UCB Pharma, research grants from Abbvie, Janssen Pharmaceutical Research & Development and UCB Pharma, and payments for lectures or speakers bureau from Abbvie, Janssen Pharmaceutical Research & Development. S.S., P.S.D., A.Z. and S.R. declare no competing interests.

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Singh, S., Dulai, P., Zarrinpar, A. et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol 14, 110–121 (2017). https://doi.org/10.1038/nrgastro.2016.181

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